Pembrolizumab In Central Nervous System Metastases

Inclusion Criteria: * Participants must have histologically or cytologically confirmed disease from any solid tumor * Participants must have measurable disease in the CNS, defined as at least one lesion that can be accurately measured in at least one dimension as ≥5 mm . * Age ≥18 years. * ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A) * Life expectancy of greater than 6 weeks * Participants must have normal organ and marrow function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation. * Adequate Organ Function Laboratory Values * Hematological \---- Absolute neutrophil count (ANC) ≥1,500 /mcL \---- Platelets ≥100,000 / mcL \---- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) * Renal \---- Serum creatinine ≤1.5 X upper limit of normal (ULN) \----- OR \---- Measured or calculated a creatinine clearance ≥60 mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl) * Hepatic \---- Serum total bilirubin ≤ 1.5 X ULN \----- OR \---- Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN \---- AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN \----- OR \---- ≤ 5 X ULN for subjects with liver metastases * Albumin \>2.5 mg/dL * Coagulation ---- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants * Creatinine clearance should be calculated per institutional standard. * Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year. * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. * Ability to understand and the willingness to sign a written informed consent document. * Stable dose of dexamethasone 2mg or less for 7 days prior to initiation of treatment * Patients may have progressive systemic disease * Patients with untreated spinal cord metastases are eligible if lesions are asymptomatic * Patients with untreated brainstem metastases are eligible if lesions are small and asymptomatic * Cohort Specific Eligibility Criteria * Cohort A: * Measurable CNS disease (one parenchymal lesion ≥5 mm) * Previously untreated asymptomatic brain metastases * Patients with newly diagnosed, previously untreated primary tumors that present with brain metastases should not forego available therapy that has demonstrated a definitive overall survival benefit as firstline therapy for metastatic disease; therefore, in cases of previously untreated systemic solid tumors only those patients for whom there is no available therapy with definitive overall survival benefit, those that have failed at least one line of prior therapy for their primary tumor, or those refusing standard therapy will be eligible for this study. Specifically, for patients with previously untreated primary tumors, the following diagnoses will be excluded: HER2-positive breast cancer; small cell lung cancer; NSCLC with targetable genomic tumor aberrations (e.g. EGFR, ALK). * Cohort B: * Measurable CNS disease (one intracranial lesion ≥5 mm) * Progressive brain metastases after prior local CNS directed therapy such as radiation or surgery as defined by: * Untreated measurable lesions in patients that have received surgery and/or SRS to one or more other lesions * Residual or progressive lesions after surgery if asymptomatic * Patients who have had prior WBRT and/or SRS and then whose lesions have progressed are eligible. Lesions treated with SRS may be eligible if there is unequivocal evidence of progression * Cohort C: \--- Carcinomatous meningitis, as defined by positive cytology * Cohort D: * Measurable CNS disease (one parenchymal lesion ≥5 mm) * 1-4 brain metastases (where stereotactic radiosurgery would be indicated) * Histologically confirmed diagnosis of melanoma Exclusion Criteria: * Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. * Participants who are receiving any other investigational agents. * Has a diagnosis of immunodeficiency. * Requires treatment with high dose systemic corticosteroids defined as dexamethasone \>2mg/day or bioequivalent within 7 days of initiating therapy. * Has received systemic immunosuppressive treatments, aside from systemic corticosteroids as described in Section 3.2.4, within three months of start of study drug * Hypersensitivity to pembrolizumab or any of its excipients * Has a known history of active TB (Bacillus Tuberculosis) * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. * HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated. * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Has known history of, or any evidence of active, non-infectious pneumonitis. * Has an active infection requiring systemic therapy. * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. * Unable to undergo brain MRI. * Participants who are receiving other concurrent chemotherapies or immunotherapies for their cancer (except for patients who will receive trastuzumab, bisphosphonates, denosumab or ovarian suppression therapy Radiation therapy to a symptomatic single metastatic site or to the brain may be allowed at the investigator's discretion). * Will need immediate local surgery or radiation for their brain metastases * Acute symptomatic CNS hemorrhage