Phase II Study of Gamma Knife Radiosurgery and Temozolomide for Brain Metastases

Inclusion Criteria: * All subjects must have history of histologically confirmed malignancy. Brain biopsy is not required unless diagnosis is judged to be in doubt by the treating physician. * Newly diagnosed brain metastases (four or fewer by thin slice post-contrast MRI). * ECOG performance status of less than or equal to 2 for patients with no prior chemotherapy, and less than or equal to 1 for patients with prior chemotherapy. * Age greater than 18 * Life expectancy greater than 12 weeks * Subjects given written informed consent * Adequate hematologic, renal and liver function as demonstrated by laboratory values performed within 14 days, inclusive, prior to administration of study drug: * Absolute neutrophil count (ANC) \>= 1500/mm3 * Platelet count \>= 100,000/mm3 * Hemoglobin \>= 9 g/dL * BUN and serum creatinine \<= 1.5 times upper limit of laboratory normal * Total and direct bilirubin \<= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, total and direct bilirubin \<=5 times upper limit of normal * SGOT and SGPT \<= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, SGOT and SGPT \<=5 times upper limit of normal * Alkaline phosphatase \<= 2 times upper limit of laboratory normal or in the presence of documented liver metastases, alkaline phosphatase of \<= 5 times upper limit of normal Exclusion Criteria: * Patients with small cell lung cancer and lymphoma are ineligible. * More than four metastases by thin slice MRI. Note that if a diagnostic study prior to radiosurgery demonstrates only four tumors but the gamma knife treatment-planning scan reveals greater than four tumors, the patients will still be eligible for the protocol if all tumors can be treated with radiosurgery. * Chemotherapy within four weeks prior to study drug administration * Patients, who in the opinion of the treating medical oncologist, require immediate cytotoxic chemotherapy other than the study drug. Allowed medications include antihormonal agents (i.e., Tamoxifen), herceptin and bisphosphonates. * Radiation therapy to greater than or equal to 50% of the bone marrow. Completion of radiation therapy less than 4 weeks prior to study drug administration for radiotherapy to \>= 15% of bone marrow and less than 2 weeks prior for radiotherapy to \< 15% of bone marrow. * Insufficient recovery from all active toxicities of prior therapies * Subjects who are poor medical risks because of non-malignant systemic disease * Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction). * Previous or concurrent malignancies at other sites, or treatment for malignancy at the site within 5 years of study start with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin. * Known HIV positively or AIDS-related illness. * Pregnant or nursing women. * Women of childbearing potential who are not using an effective method of contraception. Women of childbearing potential must have a negative serum pregnancy test 24 hours prior to administration of study drug and be practicing medically approved contraceptive precautions. * Men who are not advised to use an effective method of contraception.