Study of Intraoperative Radiotherapy for Patients With Large Brain Metastases Treated With Neurosurgical Resection

Inclusion Criteria: 1. Participants must be ≥ 18 years of age. 2. Participants must have a Karnosfky performance status of ≥ 50%. 3. Participants must not have had prior intracranial radiation. 4. Participants must have a life expectancy greater than 3 months. 5. Participants must have a preoperative MRI Brain T1-Gadolinum enhanced scan demonstrating a non-dural based lesion with greatest diameter ≥ 2.5 cm. 6. Sufficient distance (≥ 2cm) of the intracranial lesion from optic structures (optic chiasm and bilateral optic nerves) and brainstem to meet established normal structure dose limits. 7. Subject or subject's legal representative to provide signed/written informed consent to participate in the study protocol. 8. Surface of balloon applicator must be ≥ 1cm from skin overlying closest portion of calvarium. 9. Participants may remain on systemic therapy if they are receiving immunotherapy (anti-PD1, anti-PDL1, anti-CTLA-4), capecitabine, temozolomide, etoposide, vinorelbine, pemetrexed, lapatinib, traztuzumab, bevacizumab, mTor or ALK targeted agents with no break prior to initiating IORT. 9.1 Participants receiving cisplatin, methotrexate, taxanes, tyrosine kinase inhibitors, or BRAF targeted agents must have a seven day washout period prior to receiving IORT. 9.2 Participants receiving doxorubicin, T-DM1, or antibody-drug conjugates must have a fourteen day washout period prior to receiving IORT. 9.3. Participants receiving all other concurrent systemic agents will undergo consideration for a washout period prior to receiving IORT at the discretion of the study principal investigator. Exclusion Criteria: 1. Participants may not be pregnant or breast-feeding. 2. Patients must not have dural lesions or leptomeningeal disease. 3. Patients must not have psychiatric or social conditions limiting adherence to protocol guidelines. 4. Patients must not have contraindications to anesthesia, surgery, or MR imaging with Gadolinium injection. 5. Patients must not have a frozen section diagnosis of small cell carcinoma, lymphoma, germinoma or non-malignant histology. 6. Patients with additional unresected brain metastases must have a limited number of lesions/or volume of intracranial disease amenable to stereotactic radiotherapy at the discretion of the study principal investigator. 7. Patients deemed to require postoperative whole brain radiotherapy should be excluded.