So there are two different things that can be done:
Unplug the whole CD/DVD-ROM device so that the VM does not even sees the device at all, that can only be done live (hot-unplugged) if the underlying device-bus supports it, i.e., it will work for SCSI but not for the default IDE.
Eject the CD/DVD from the device, that is normally always support, independent of what device-bus is configured. Just select the CD/DVD-ROM device and click Edit (or double click it) and select "do not use any media" and confirm with "Ok", that should eject the ISO-image from the CD/DVD-ROM drive.
I am probably missing something. May I ask how do I achieve option #1. I do not see the option to add SCSI so I can mount an ISO image to it. Below are the only options that I see.
For option #2 that you described, wouldn't this require a bounce of the virtual machine for changes to take effect?