Comparing Single vs Multiple Dose Radiation for Cancer Patients With Brain Metastasis and Receiving Immunotherapy

Inclusion Criteria: * At least one intact brain metastasis or resection cavity ≥ 2 cm in diameter or ≥ 4 cc volume. * Patients at initial diagnosis of brain metastases and patients with known brain metastasis treated with systemic therapy alone are eligible. * Patients who have previously undergone SRS for brain metastases are eligible if all MRIs and DICOM-RT files from prior SRS courses are available for upload to TRIAD and there are no lesions requiring re-irradiation. Prior SRS data upload is NOT required prior to enrollment and randomization. Both SSRS and FSRS are acceptable. * Lesion volume will be approximated by measuring the lesion's three perpendicular diameters on contrast-enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g., xyz/2). Alternatively, direct volumetric measurements via slice-by-slice contouring on a treatment planning software package can be used to calculate the total tumor volume. * Any extent of non-CNS disease is allowed. There is no requirement for non-CNS disease to be controlled prior to study entry. * For patients considered to be borderline or potentially eligible by size or volume criteria, sites have the option to send in DICOM films for central review screening. * Age ≥ 18 years at the time of enrollment. * Total number of brain metastases (including resection cavities) ≤ 15 on diagnostic MRI; all lesions must be amenable to SSRS and FSRS as determined by the tre…