Randomized, post-market multi-center study investigating the efficacy of two sets of treatment algorithms in brain metastases (BM) patients at the time of first intervention for radiographic progression after stereotactic radiosurgery (SRS), with or without surgery.

Inclusion Criteria:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. Patients with radiographically proven (by gadolinium-enhanced [Gd-] MRI) parenchymal brain metastases from histologically confirmed non-central nervous system (CNS) cancer.

2. Patients with a "targetable", bidimensionally-measurable, intracranial lesion that is radiographically recurrent after previous treatment with SRS +/- surgery (craniotomy or LITT). To classify a lesion as radiographically progressive, the lesion must demonstrate a ≥ 25% increase in size following treatment based on the Neuro-Oncology Criteria of Tumor Response for CNS Tumors. To be "targetable" for this study, the lesion should be coverable through a planned single LITT trajectory and thus have a maximum perpendicular diameter (perpendicular to the laser trajectory) of 3 cm. An intra-operative decision to utilize two trajectories is acceptable and patient may remain on study.

3. Patient must be at least 3 months post initial SRS treatment of the target lesion

4. Target lesion must be amenable to undergo surgical biopsy and LITT treatment as determined by the treating neurosurgeon.

5. Frozen pathology diagnosis must be attainable.

6. Patient must be symptomatically stable for a minimum of 3 days prior to the procedure date on a on a max total daily steroid dose equivalent to 4mg of Dexamethasone.

7. ≥18 years of age

8. KPS ≥70

9. Patient is able and willing to complete study requirements

10. Patients with adequate hematologic parameters (all tests to be performed within <4 weeks of biopsy):

    1. ANC ≥ 1.5 X 109/L
    2. Platelet count ≥ 100 x 109/L

11. Blood chemistry laboratory value for serum creatinine < 1.5 x ULN (test to be performed within <4 weeks of biopsy)

12. Female patients must have a negative serum pregnancy test at screening. (Not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal)

13. All patients of reproductive potential must agree to use an effective method of contraception during the study

14. Patients must be accessible for follow-up

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Patients with greater than 3 progressing lesions at time of enrollment. To classify as a radiographically progressive, lesion must demonstrate a ≥ 25% increase in size following treatment based on the RANO criteria. Of note, there is no exclusion for total number of metastases. However, only one lesion can be selected to be the targeted lesion and this lesion alone may be ablated during the study procedure.
2. Patients with concomitant newly diagnosed intracranial metastases (concurrent with the targetable radiographically progressive lesion), as these will require prioritized and different treatment approaches.
3. Prior bevacizumab use within 4 weeks of study initiation
4. Patients with additional concurrent malignancies requiring active treatment, except non-melanoma skin cancer, or in-situ cancer of the cervix
5. Patients with a serious active infection or other serious underlying medical conditions that would impair the ability of the patient to complete the protocol related QOL questionnaires and cognition assessments
6. Inability to tolerate or contraindication to steroid therapy (i.e., dexamethasone)
7. Deemed ineligible or unable to tolerate SRS therapy by treating neurosurgeon and/or radiation oncologist
8. Patients with any condition that would prohibit them from undergoing a surgical procedure, at the discretion of the treating physician team
9. Patients unwilling or unable to give consent for participation
10. Patients unable to comply with study requirements
11. Patients with diffuse leptomeningeal disease
12. Patients with rapidly progressing extracranial disease