Systems for planning delivery of radiation dose to a target region within a subject comprise a processor configured to: iteratively optimize a simulated dose distribution relative to a set of one or more optimization goals comprising a desired dose distribution in the subject over a first plurality of control points located on a trajectory, the trajectory comprising relative movement between a treatment radiation source and the subject; reach one or more initial termination conditions, and after reaching the one or more initial termination conditions: specify a second plurality of control points along the trajectory, the second plurality of control points comprising a larger number control points than the first plurality of control points; and iteratively optimize a simulated dose distribution relative to the set of one or more optimization goals over the second plurality of control points to thereby determine a radiation delivery plan.